alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs.

alpha-Melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide derived from the proopiomelanocortin by post-translational processing. In addition to its effects on melanocytes, alpha-MSH has potent anti-inflammatory effects when administered systemically or locally. The anti-inflammatory effects of alpha-MSH are mediated by direct effects on cells of the immune system as well as indirectly by affecting the function of resident non-immune cells. alpha-MSH affects several pathways implicated in regulation of inflammatory responses such as NF-kappaB activation, expression of adhesion molecules and chemokine receptors, production of pro-inflammatory cytokines and other mediators. Thus alpha-MSH may modulate inflammatory cell proliferation, activity and migration. The anti-inflammatory effects of alpha-MSH have been confirmed by means of animal models of inflammation such as irritant and allergic contact dermatitis, cutaneous vasculitis, asthma, inflammatory bowel disease, rheumatoid arthritis, ocular and brain inflammation. Most of the anti-inflammatory activities of alpha-MSH can be attributed to its C-terminal tripeptide KPV. K(D)PT, a derivative of KPV corresponding to the amino acid 193-195 of IL-1beta, is currently emerging as another tripeptide with potent anti-inflammatory effects. The anti-inflammatory potential together with the favourable physiochemical properties most likely will allow these agents to be developed for the treatment of inflammatory skin, eye and bowel diseases, allergic asthma and arthritis.